Differential distribution and function of hyperpolarization-activated channels in sensory neurons and mechanosensitive fibers
Differential distribution and function of hyperpolarization-activated channels in sensory neurons and mechanosensitive fibers
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DOI：
10.1523/jneurosci.5156-03.2004
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发表时间：
2004-03-31
影响因子：
5.3
通讯作者：
Kunze, DL
中科院分区：
文献类型：
--
作者：
Doan, TN;Stephans, K;Kunze, DL
感觉神经元表达的超极化激活电流（I-H）在种群内的幅度和动力学不同。我们研究了这些差异的结构基础，并探讨了从大鼠结状神经节分离的感觉神经元的I-H通道的功能作用。免疫组织化学研究表明，超极化激活的环核苷酸门控（HCN）蛋白（HCN 1，HCN 2，HCN 4）的感觉神经元和外周终末的差异分布。HCN 2和HCN 4免疫反应性存在于所有结状神经元。相比之下，只有20%的总人口表达HCN 1免疫反应性。HCN 1没有与IB 4（C型神经元的标志物）共定位，只有15%的HCN 1阳性神经元与香草素受体VR 1（另一种主要与C型神经元相关的蛋白质）的免疫反应性共定位。因此，大多数含HCN 1的神经元是A型神经元。在进一步的支持，HCN 1是存在于有髓但不无髓感觉纤维的机械敏感性终端，而HCN 2和HCN 4是存在于有髓和无髓纤维的受体终端。在电压钳研究中，细胞渗透cAMP类似物移动激活曲线I-H去极化电位在C型神经元，但不是A型神经元。在电流钳记录中，CsCl仅抑制结状神经元中的I-H，使静息膜电位从-63 +/- 1超极化至-73 +/-2 mV，并且使输入电阻从1.3 Gohm几乎加倍至2.2 Gohm。此外，在CsCl存在下，在较低去极化电流注射下启动动作电位。在感觉感受器末端，CsCl降低机械感受器放电起始的阈值压力。因此，I-H的消除增加了索马和外周感觉末梢的兴奋性。
Sensory neurons express hyperpolarization-activated currents (I-H) that differ in magnitude and kinetics within the populations. We investigated the structural basis for these differences and explored the functional role of the I-H channels in sensory neurons isolated from rat nodose ganglia. Immunohistochemical studies demonstrated a differential distribution of hyperpolarization-activated cyclic nucleotide-gated (HCN) protein (HCN1, HCN2, HCN4) in sensory neurons and peripheral terminals. HCN2 and HCN4 immunoreactivity was present in all nodose neurons. In contrast, only 20% of the total population expressed HCN1 immunoreactivity. HCN1 did not colocalize with IB4 (a marker for C-type neurons), and only 15% of HCN1-positive neurons colocalized with immunoreactivity for the vanilloid receptor VR1, another protein associated primarily with C-type neurons. Therefore, most HCN1-containing neurons were A-type neurons. In further support, HCN1 was present in the mechanosensitive terminals of myelinated but not unmyelinated sensory fibers, whereas HCN2 and HCN4 were present in receptor terminals of both myelinated and unmyelinated fibers. In voltage-clamp studies, cell permeant cAMP analogs shifted the activation curve for I-H to depolarized potentials in C-type neurons but not A-type neurons. In current-clamp recording, CsCl, which inhibits only I-H in nodose neurons, hyperpolarized the resting membrane potential from -63 +/- 1 to -73 +/- 2mV and nearly doubled the input resistance from 1.3 to 2.2 GOhm. In addition, action potentials were initiated at lower depolarizing current injections in the presence of CsCl. At the sensory receptor terminal, CsCl decreased the threshold pressure for initiation of mechanoreceptor discharge. Therefore, elimination of the I-H increases excitability of both the soma and the peripheral sensory terminals.